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The Journal of Neuroscience, May 17, 2006, 26(20):5500-5510; doi:10.1523/JNEUROSCI.3955-05.2006

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Behavioral/Systems/Cognitive
Urocortin 2-Deficient Mice Exhibit Gender-Specific Alterations in Circadian Hypothalamus–Pituitary–Adrenal Axis and Depressive-Like Behavior

Alon Chen,¹ Eric Zorrilla,² Sean Smith,¹ David Rousso,¹ Coree Levy,² Joan Vaughan,¹ Cindy Donaldson,¹ Amanda Roberts,¹ Kuo-Fen Lee,¹ and Wylie Vale¹

¹Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037, and ²Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037

Correspondence should be addressed to Dr. Wylie Vale, Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037. Email: vale{at}salk.edu

Gender differences in hypothalamus–pituitary–adrenal (HPA) axis activation and the prevalence of mood disorders are well documented. Urocortin 2, a recently identified member of the corticotropin-releasing factor family, is expressed in discrete neuroendocrine and stress-related nuclei of the rodent CNS. To determine the physiological role of urocortin 2, mice null for urocortin 2 were generated and HPA axis activity, ingestive, and stress-related behaviors and alterations in expression levels of CRF-related ligands and receptors were examined. Here we report that female, but not male, mice lacking urocortin 2 exhibit a significant increase in the basal daily rhythms of ACTH and corticosterone and a significant decrease in fluid intake and depressive-like behavior. The differential phenotype of urocortin 2 deficiency in female and male mice may imply a role for urocortin 2 in these gender differences.

Key words: urocortin 2; CRF/CRH; depression; gender differences; stress; HPA axis

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Received Sept. 19, 2005; revised March 19, 2006; accepted April 10, 2006.

Correspondence should be addressed to Dr. Wylie Vale, Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037. Email: vale{at}salk.edu

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				M. Fukui, R. M. Rodriguiz, J. Zhou, S. X. Jiang, L. E. Phillips, M. G. Caron, and W. C. Wetsel Vmat2 Heterozygous Mutant Mice Display a Depressive-Like Phenotype J. Neurosci., September 26, 2007; 27(39): 10520 - 10529. [Abstract] [Full Text] [PDF]

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